This research Center was originally funded in 1987. The Center funding provided support for a Core Unit to coordinate Center activities and initiate new projects using flexible funding for pilot projects. Specific research projects were also funded within the Center. The "center concept" has functioned very well in that the Center funding has been used to stimulate growth and productivity. Not only have the specific projects been completed, but new projects which began as pilot projects were completed and others were developed into new grant applications. The educational program has grown and there now is an institutional fellowship program that has attracted high quality applicants including a high proportion of physicians. An Institutional Physician Scientist Development program has just been awarded for new faculty level development. A 21 hour required course on substance abuse for medical students has been instituted. A Treatment Research Unit has been created that has expanded our research population to the non-veteran community. We have just been awarded an Instrument Development Center that will coordinate with this Research Center to facilitate the development of new clinical research instruments. A Scientific Advisory Board was formed and it has met annually since the founding of the Center. Over the past five years, the Center staff have published 145 research reports, 79 reviews and 2 books. Studies completed by Center staff have been utilized by policy markers in Congressional testimony. These include a controlled study of the effects of three levels of psychosocial intervention in combination with methadone treatment, a longitudinal study of HIV conversion rates in opiate addicts in and out of treatment, a study of the efficacy of inpatient and outpatient rehabilitation for cocaine dependence and a controlled study of the effects of naltrexone treatment on reincarceration rate for Federal probationers. The present application is for an additional five years of funding. In addition to continuing the Core Unit at approximately the same level, we are requesting funding for new projects that will address current problems of intravenous drug abuse. The first section addresses the biological basis of relapse to drug dependence. The first utilizes new brain imaging techniques in human subjects to extend our prior findings concerning conditioning in cocaine dependence. The second combines microdialysis and behavioral techniques in an animal model of cocaine dependence. The third project continues our work on endogenous opioids in a series of proposed studies of tolerance and dependence using animal models and isolated cells and in studies of human opiate addicts at specific stages of the addiction cycle. Section 2 consists of three projects dealing with relapse to drug dependence. The first compares levels of psychosocial intervention in combination with medication for the treatment of cocaine dependence. The second compares two types of aftercare over 24 months of followup for the treatment of cocaine dependence. The third study examines the relationship between psychopathology and treatment response in women substance abusers over a two year followup period.